Klebanoff S J, Waltersdorph A M
Department of Medicine, University of Washington, Seattle 98195.
J Exp Med. 1990 Nov 1;172(5):1293-303. doi: 10.1084/jem.172.5.1293.
Acceleration of the autoxidation of Fe2+ by apotransferrin or apolactoferrin at acid pH is indicated by the disappearance of Fe2+, the uptake of oxygen, and the binding of iron to transferrin or lactoferrin. The product(s) formed oxidize iodide to an iodinating species and are bactericidal to Escherichia coli. Toxicity to E. coli by FeSO4 (10(-5) M) and human apotransferrin (100 micrograms/ml) or human apolactoferrin (25 micrograms/ml) was optimal at acid pH (4.5-5.0) and with logarithmic phase organisms. Both the iodinating and bactericidal activities were inhibited by catalase and the hydroxyl radical (OH.) scavenger mannitol, whereas superoxide dismutase was ineffective. NaCl at 0.1 M inhibited bactericidal activity, but had little or no effect on iodination. Iodide increased the bactericidal activity of Fe2+ and apotransferrin or apolactoferrin. The formation of OH.was suggested by the formation of the OH.spin-trap adduct (5,5-dimethyl-1-pyroline N-oxide [DMPO]/OH)., with the spin trap DMPO and the formation of the methyl radical adduct on the further addition of dimethyl sulfoxide. (DMPO/OH).formation was inhibited by catalase, whereas superoxide dismutase had little or no effect. These findings suggest that Fe2+ and apotransferrin or apolactoferrin can generate OH.via an H2O2 intermediate with toxicity to microorganisms, and raise the possibility that such a mechanism may contribute to the microbicidal activity of phagocytes.
在酸性pH条件下，脱铁转铁蛋白或脱铁乳铁蛋白对Fe2+自氧化的加速作用表现为Fe2+的消失、氧气的摄取以及铁与转铁蛋白或乳铁蛋白的结合。所形成的产物能将碘化物氧化成碘化物物种，并对大肠杆菌具有杀菌作用。FeSO4（10^(-5) M）与人脱铁转铁蛋白（100微克/毫升）或人脱铁乳铁蛋白（25微克/毫升）对大肠杆菌的毒性在酸性pH（4.5 - 5.0）和对数生长期的生物体中最为显著。碘化和杀菌活性均受到过氧化氢酶和羟基自由基（OH·）清除剂甘露醇的抑制，而超氧化物歧化酶则无效。0.1 M的NaCl抑制杀菌活性，但对碘化作用影响很小或没有影响。碘化物增强了Fe2+与脱铁转铁蛋白或脱铁乳铁蛋白的杀菌活性。通过与自旋捕获剂5,5 - 二甲基 - 1 - 吡咯啉N - 氧化物（DMPO）形成OH自旋捕获加合物（DMPO/OH·）以及在进一步添加二甲基亚砜时形成甲基自由基加合物，提示了OH·的形成。（DMPO/OH·）的形成受到过氧化氢酶的抑制，而超氧化物歧化酶影响很小或没有影响。这些发现表明，Fe2+与脱铁转铁蛋白或脱铁乳铁蛋白可通过H2O2中间体产生对微生物有毒性的OH·，并增加了这种机制可能有助于吞噬细胞杀菌活性的可能性。
